FDA approves all-oral combo therapy for previously untreated CLL
Venclexta-Calquence combination becomes 1st all-oral, fixed-duration treatment
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The U.S. Food and Drug Administration (FDA) has approved the combination of two oral therapies, Venclexta (venetoclax) and Calquence (acalabrutinib), for previously untreated adults with chronic lymphocytic leukemia (CLL), a form of blood cancer.
The newly approved combination is the first all-oral, fixed-duration regimen for previously untreated CLL in the U.S., according to Venclexta‘s maker Abbvie. The combination therapy was approved in Europe, where Venclexta is sold as Venclyxto, last year.
“This FDA approval marks a significant milestone for AbbVie and, more importantly, for people living with CLL,” Svetlana Kobina, vice president, global medical affairs, oncology at Abbvie, said in a company press release. “As the first and only all-oral, fixed-duration combination regimen for previously untreated patients, the Venclexta plus [Calquence] approval expands choice and flexibility for patients and providers navigating complex treatment decisions in CLL.”
CLL is a form of blood cancer in adults characterized by the uncontrolled growth of B-cells, a type of immune cell. Venclexta is designed to block the activity of B-cell lymphoma-2 (BCL-2), a protein that helps cancerous cells to resist apoptosis (programmed cell death). Meanwhile, Calquence, which is sold by AstraZeneca, works to block the activity of Bruton’s tyrosine kinase (BTK), a signaling protein that helps drive B-cell activity.
“With the FDA approval of the combination of [Venclexta and Calquence] for use as a front-line therapy in CLL, patients in the USA now have an all oral, time-limited option that can be important for many in choosing their treatment,” said Brian Koffman, MD, co-founder and chief medical officer emeritus at the CLL Society. “CLL Society is pleased to see the number of choices available for patients growing.”
Trial data support approval
The FDA’s approval of the combination therapy was based mainly on data from the Phase 3 AMPLIFY clinical trial (NCT03836261), which tested Venclexta plus Calquence against a doctor’s choice of approved chemoimmunotherapy regimens (treatments that combine chemotherapies with immune-modulating drugs).
Results showed that the risk of disease progression or death was significantly reduced, by about 35%, in patients given Venclexta and Calquence. Most patients given chemoimmunotherapy died or experienced disease progression within about four years of starting treatment, whereas most patients given Venclexta plus Calquence were still alive and free from disease progression at the same time point.
Safety data from patients treated with Venclexta and Calquence were broadly consistent with the known safety profiles of each medication when used individually. Common side effects of the combo include low immune cell counts, headache, diarrhea, musculoskeletal pain, and COVID-19. Series side effects, including low immune counts, COVID-19, and secondary cancers, were reported in 2% or more of patients.
